Similar Datasets
Project description:Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social communication deficits and repetitive behaviors. MicroRNAs (miRNAs) have been recently recognized as potential biomarkers of ASD as they are dysregulated in various tissues of individuals with ASD. However, it remains unclear whether miRNA expression is altered in individuals with high-functioning ASD. Here, we investigated the miRNA expression profile in peripheral blood from adults with high-functioning ASD, and age and gender-matched healthy controls. Our findings may provide insights regarding the molecular clues for recognizing high-functioning ASD.
2020-05-03 | GSE89596 | GEO
Project description:Whole-exome sequencing studies have implicated chromatin modifiers and transcriptional regulators in autism spectrum disorder (ASD) through the identification of de novo loss of function mutations in affected individuals. Many of these genes are co-expressed in mid-fetal human cortex, suggesting ASD risk genes converge in regulatory networks that are perturbed in ASD during neurodevelopment. To elucidate such networks we mapped promoters and enhancers bound by the chromodomain helicase CHD8, which is strongly enriched in ASD-associated de novo loss of function mutations, using ChIP-seq in mid-fetal human brain, human neural stem cells (hNSCs), and embryonic mouse cortex. We find that CHD8 targets are strongly enriched for ASD risk genes that converge in ASD-associated co-expression networks in human midfetal cortex. CHD8 knockdown in hNSCs results in significant dysregulation of ASD risk genes targeted by CHD8, as well as additional genes important for neurodevelopment, including members of the Wnt/β-catenin signaling pathway. Integration of CHD8 binding data with genetic and gene co-expression data in ASD risk models provides support for additional ASD risk genes. Together, our results suggest that loss of CHD8 function contributes to ASD through regulatory perturbation of other ASD risk genes during human cortical development.
2015-01-21 | GSE57369 | GEO
Project description:The autism spectrum disorders (ASD) are a collection of disorders with heterogeneous etiology, exhibiting common traits including impaired social interactions and communications, repetitive behaviors. 15q11-q13 copy number variations (CNV) were found in 1-3% of ASD cases; of which the detailed mechanism of the major contributor UBE3A gene acted still remained elusive. Here we identified a key enzyme in RA synthesis, negatively regulated in ubiquitination-dependent mode promoted by UBE3A. Our data provide evidences linking UBE3A hyperactivity with ASD phenotypes, with implications for understanding ASD etiology and providing potential interventions in ASD clinical therapy.
2017-12-28 | GSE93207 | GEO
Project description:Exosomes have been demonstrated to exert momentous roles in autism spectrum disorder (ASD). In this study, we aimed to make contribution to understanding pathogenesis of ASD and screen for the potential biomarkers associated with the occurrence and development of ASD.
2024-03-27 | GSE222046 | GEO
Project description:Autism spectrum disorder (ASD) is a complex heterogeneous developmental disease with a significant genetic background that is frequently caused by rare copy number variants (CNV). The aim of the study was to identify new candidate genes for ASD in the studied cohort of ASD-diagnosed patients. We used chromosomal microarray analysis (CMA) - a Cytoscan HD (Affymetrix, Santa Clara, CA, USA) to detect CNV in 87 ASD patients and their relatives and evaluated their clinical significance. Pathogenic and likely pathogenic mutations were identified by CMA in 8 and 9 ASD patients, respectively. CMA revealed 89 rare CNV: 8 pathogenic, 12 designated VOUS - likely pathogenic, 12 VOUS - uncertain, and 57 VOUS - likely benign or benign. CNV (pathogenic/VOUS-likely pathogenic/VOUS - uncertain) overlapping the same gene in more than one patient were observed in DOCK8 gene and PARK2 gene. This work presents new evidence about the possible roles of PARK2 and DOCK8 in the etiology of ASD, and suggests CTNNA2 as a candidate gene for ASD risk.
2018-05-25 | GSE114870 | GEO
Project description:Autism spectrum disorders (ASD) are characterized by a high degree of genetic heterogeneity. Genomic studies identified common pathological processes underlying the heterogeneous clinical manifestations of ASD, and transcriptome analyses revealed that gene networks involved in synapse development, neuronal activity and immune function are deregulated in ASD. Mouse models provide unique tools to investigate the neurobiological basis of ASD. Here we used the BTBR (BTBR T+ Itpr3tf/J) ASD mouse model to identify conserved ASD-related molecular signatures. Gene expression in the BTBR mouse prefrontal cortex was measured by microarrays and compared to the gene expression profile of C57Bl6/J controls (5 months old, n= 3 mice per group).
2016-05-18 | E-GEOD-81502 | biostudies-arrayexpress
Project description:Autism spectrum disorders (ASD) are characterized by a high degree of genetic heterogeneity. Genomic studies identified common pathological processes underlying the heterogeneous clinical manifestations of ASD, and transcriptome analyses revealed that gene networks involved in synapse development, neuronal activity and immune function are deregulated in ASD. Mouse models provide unique tools to investigate the neurobiological basis of ASD. Here we used the BTBR (BTBR T+ Itpr3tf/J) ASD mouse model to identify conserved ASD-related molecular signatures. Gene expression in the BTBR mouse hippocampus was measured by microarrays and compared to the gene expression profile of C57Bl6/J controls (5 months old, n= 4 mice per group).
2016-05-18 | E-GEOD-81501 | biostudies-arrayexpress
Project description:Whole-exome sequencing studies have implicated chromatin modifiers and transcriptional regulators in autism spectrum disorder (ASD) through the identification of de novo loss of function mutations in affected individuals. Many of these genes are co-expressed in mid-fetal human cortex, suggesting ASD risk genes converge in regulatory networks that are perturbed in ASD during neurodevelopment. To elucidate such networks we mapped promoters and enhancers bound by the chromodomain helicase CHD8, which is strongly enriched in ASD-associated de novo loss of function mutations, using ChIP-seq in mid-fetal human brain, human neural stem cells (hNSCs), and embryonic mouse cortex. We find that CHD8 targets are strongly enriched for ASD risk genes that converge in ASD-associated co-expression networks in human midfetal cortex. CHD8 knockdown in hNSCs results in significant dysregulation of ASD risk genes targeted by CHD8, as well as additional genes important for neurodevelopment, including members of the Wnt/M-NM-2-catenin signaling pathway. Integration of CHD8 binding data with genetic and gene co-expression data in ASD risk models provides support for additional ASD risk genes. Together, our results suggest that loss of CHD8 function contributes to ASD through regulatory perturbation of other ASD risk genes during human cortical development. Two biological replicates for each ChIP with appropriate Input control Four biological replicates for each condition in knockdown experiments (Ctrl construct, Chd8 target C, and Chd8 target G)
2015-01-21 | E-GEOD-57369 | biostudies-arrayexpress
Project description:Exome sequencing studies have identified multiple genes harboring de novo loss-of-function (LoF) variants in individuals with autism spectrum disorders (ASD), including TBR1, a master regulator of cortical development. We performed ChIP-seq for TBR1 during mouse cortical neurogenesis and show that TBR1-bound regions are enriched adjacent to ASD genes. ASD genes were also enriched among genes that are differentially expressed in Tbr1 knockouts, which together with the ChIP-seq data, suggests direct transcriptional regulation. Of the 9 ASD genes examined, 7 were misexpressed in the cortices of Tbr1 knockout mice, including 6 with increased expression in the deep cortical layers. ASD genes with adjacent cortical TBR1 ChIP-seq peaks also showed unusually low levels of LoF mutations in a reference human population and among Icelanders. We then leveraged TBR1 binding to identify an appealing subset of candidate ASD genes. Our findings highlight a TBR1-regulated network of ASD genes in the developing neocortex that are relatively intolerant to LoF mutations, indicating that these genes may play critical roles in normal cortical development.
2016-06-17 | GSE71384 | GEO